The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation

Ho Soo Lee, Zhonghui Lin, Sunyoung Chae, Young Suk Yoo, Byung Gyu Kim, Youngsoo Lee, Jared L. Johnson, You Sun Kim, Lewis C. Cantley, Chang Woo Lee, Hongtao Yu, Hyeseong Cho

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Chromatin remodelers regulate the nucleosome barrier during transcription, DNA replication, and DNA repair. The chromatin remodeler RSF1 is enriched at mitotic centromeres, but the functional consequences of this enrichment are not completely understood. Shugoshin (Sgo1) protects centromeric cohesion during mitosis and requires BuB1-dependent histone H2A phosphorylation (H2A-pT120) for localization. Loss of Sgo1 at centromeres causes chromosome missegregation. Here, we show that RSF1 regulates Sgo1 localization to centromeres through coordinating a crosstalk between histone acetylation and phosphorylation. RSF1 interacts with and recruits HDAC1 to centromeres, where it counteracts TIP60-mediated acetylation of H2A at K118. This deacetylation is required for the accumulation of H2A-pT120 and Sgo1 deposition, as H2A-K118 acetylation suppresses H2A-T120 phosphorylation by Bub1. Centromeric tethering of HDAC1 prevents premature chromatid separation in RSF1 knockout cells. Our results indicate that RSF1 regulates the dynamics of H2A histone modifications at mitotic centromeres and contributes to the maintenance of chromosome stability.

Original languageEnglish (US)
Article number3848
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Lee, H. S., Lin, Z., Chae, S., Yoo, Y. S., Kim, B. G., Lee, Y., Johnson, J. L., Kim, Y. S., Cantley, L. C., Lee, C. W., Yu, H., & Cho, H. (2018). The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation. Nature communications, 9(1), [3848]. https://doi.org/10.1038/s41467-018-06377-w